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Clinical Research

A randomized, phase II study of pazopanib in castrate-sensitive prostate cancer: a University of Chicago Phase II Consortium/Department of Defense Prostate Cancer Clinical Trials Consortium study

Prostate Cancer and Prostatic Diseases volume 15, pages 87–92 (2012)Cite this article

Abstract

Background:

Intermittent androgen suppression (IAS) is an increasingly popular treatment option for castrate-sensitive prostate cancer. On the basis of previous data with anti-angiogenic strategies, we hypothesized that pan-inhibition of the vascular endothelial growth factor receptor using pazopanib during the IAS off period would result in prolonged time to PSA failure.

Methods:

Men with biochemically recurrent prostate cancer, whose PSA was <0.5 ng ml−1 after 6 months of androgen deprivation therapy were randomized to pazopanib 800 mg daily or observation. The planned primary outcome was time to PSA progression >4.0 ng ml−1.

Results:

Thirty-seven patients were randomized. Of 18 patients randomized to pazopanib, at the time of study closure, 4 had progressive disease, 1 remained on treatment and 13 (72%) electively disenrolled, the most common reason being patient request due to grade 1/2 toxicity (8 patients). Two additional patients were removed from treatment due to adverse events. Of 19 patients randomized to observation, at the time of study closure, 4 had progressive disease, 7 remained under protocol-defined observation and 8 (42%) had disenrolled, most commonly due to non-compliance with protocol visits (3 patients). Because of high dropout rates in both arms, the study was halted.

Conclusions:

IAS is a treatment approach that may facilitate investigation of novel agents in the hormone-sensitive state. This trial attempted to investigate the role of antiangiogenic therapy in this setting, but encountered several barriers, including toxicities and patient non-compliance, which can make implementation of such a study difficult. Future investigative efforts in this arena should carefully consider drug toxicity and employ a design that maximizes patient convenience to reduce the dropout rate.

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Acknowledgements

This study was supported in part by the NCI Early Therapeutics Development with Phase II emphasis grant: N01-CM-62201 and DOD Prostate Cancer Training Award: W81XWH-08-PCRP-PRTA.

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Authors and Affiliations

  1. Department of Medicine, Section of Hematology/Oncology, University of Chicago, Chicago, IL, USA

    J E Ward, T Karrison, R Z Szmulewitz, P H O'Donnell, W M Stadler & E M Posadas

  2. Division of Hematology/Oncology, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA

    G Chatta

  3. Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA

    M Hussain

  4. Northshore University Health System, Evanston, IL, USA

    D Shevrin

  5. Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA

    E M Posadas

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  1. J E Ward
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Correspondence to E M Posadas.

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Competing interests

Dr Posadas has received compensation from GlaxoSmithKline as a member of their speaker's bureau. Drs Ward, Karrison, Chatta, Hussain, Shevrin, Szmulewitz, O’Donnell and Stadler have nothing to disclose.

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Ward, J., Karrison, T., Chatta, G. et al. A randomized, phase II study of pazopanib in castrate-sensitive prostate cancer: a University of Chicago Phase II Consortium/Department of Defense Prostate Cancer Clinical Trials Consortium study. Prostate Cancer Prostatic Dis 15, 87–92 (2012). https://doi.org/10.1038/pcan.2011.49

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